Features of PLAP expression in placental structures during...

Features of PLAP expression in placental structures during allogeniec pregnancy (surrogate maternity, oocyte donation) on the background of pre-eclampsia, as an indicator of exosomal trophoblastactivity

Rudenko E.Е., E.A. Kogan, T.A. Demura, N.S. TrifonovaN.V. ZharkovFirst Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)2019

Allogeneic pregnancy

Age 29,43,19

A history of successful pregnancies

Somatically HEALTHY

Threats and preterm birth(43,3% 54,3%)

HIP and PE (15.4%)

surrogate maternity

Age 42,73,91

First birth or\and first pregnancy

Somatic history (including autoimmune and cardiovascular diseases)

Threats and preterm birth (11.3% 45.4%)

HIP and PE (24%)

egg donation

The theory of pathogenesis of PE associated with exosomes

Exosomes

https://doi.org/10.3390/cells8060558

Aim of study

To Investigate the exosomal activity of trophoblast in the norm and with the preeclampsia in allogeneic pregnancy

pregnant women after IVF with

donor egg

N=89

morphological verification

placentas/placental bed

N=47 (SM)

IGH without PE

N=18

IGH wit PE

N=8

morphological verification

placentas/placental bed

N=42 (OD)

IGH without PE

N=21

IGH wit PE

N=12

Inclusion сriteria•IVF with a donor egg •Single pregnancy• Gestational age> 20 weeks•Clinically confirmed development of pre-eclampsia (all degrees of severity

Exclusion criteria: •Multiple pregnancy• Severe extragenital pathology •Gestational age <20 weeks •Complications of pregnancy with well-studied pathogenesis (APS, hereditary forms of thrombophilia, etc.)

Material

Methods

1. Сlinical and laboratory analysis (HLA II detection)

2. Morphological verification

- Histological study paraffin sections of placenta and placental bed, staining PAS, Orcein, hematoxylin and eosin.

- Immunohistochemical study of placenta and placental bed paraffin sections

• monoclonal mouse anti-human PLAP (Dako)

• monoclonal mouse anti-human CD9 (Dako)

• mouse anti-human CD81 (Dako)

- Mophrometric analysis of optical density (ImageM 2.0)

- Electron microscopy

Results. Somatic history and obstetric complications

0 5 10 15 20 25

Cardiovascular disease

Urinary system diseases

Respiratory diseases

Endocrine diseases

Diseases of the hepatobiliary system

The threat in the I trimester

The threat in the II trimester

The threat in the III trimester

GDM

HIP

PE

Premature placental abruption

Premature birth

OE (n=21)

SM(n=47)

OD (n=42)

Results. Morphological changes in placenta in AP with PE

01234

SM OD OE SM OD OE

N PE

Perivillous fibrioniod with LGI, H&E, x200

00,5

11,5

22,5

3

SM OD OE SM OD OE

N PE

Lymphoplasmacytic deciduitis, H&E, x400

0

1

2

3

SM OD OE SM OD OE

N PE

Massive deposits of fibrinoid in the uteroplacental region,

HE, x400

Results. Morphological changes in placental bed in AP with PE

01234

SM OD OE SM OD OE

N PE

Perivascular infiltration in placental bed,

H&E, x400

0 50 100 150

SM

OD

OE

SM

OD

OE

NP

E

Completeremodeling of thespiral arteries (%)

Partial remodelingof the spiralarteries (%)

Lack of remodeling(%)

Expression of exosome markers in villous trophoblast

0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9

SM

OD

OE

SM

OD

OE

NP

E

CD81

CD9

PLAP

PLAPCD9CD81

0 0,02 0,04 0,06 0,08 0,1 0,12

SM

OD

OE

SM

OD

OE

NP

E

CD81

CD9

PLAP

Expression of exosome markers in placental bed

CD81 CD9 PLAP

Syncytiotrophoblast, brush border

↓PLAP ↓CD9 ↓CD81relate to↓ exosome secretion, containing miRNA-127-5p and etc.

disruption of immunological tolerance

damage to the trophoblast by the mother’s immune system

↓ PIGF5 ↑ proinflammatory cytokines6

↓sFLT↓sEng7

Preeclampsia

↑ Th1 \ ↓ Th2 1

↑cytotoxic NK 2

↓apoptosis of maternal T cells through FasL and TRAIL 3

↓ activation tTreg 4

1. Redman et al. 2012; 2. Shomer et al. 2013; 3 .Lee et al. 2012; 4. .Vargas et al. 2014 ; 5.Vargas et al. 2009; 6.Salomon et al. 2014

7.Lundholm et al. 2014

Conclusions• Placentas and placental beds in the allogeneic pregnancy are characterized by pronounced

signs of immune alteration of the placenta. The pathology of the placental bed consists in chronic inflammation in the perivascular region and a violation of the remodeling of the spiral arteries.

• PLAP, CD9 and CD81 were found in the cells of the syncytiotrophoblast villi, parietal trophoblast and single cells of the extravillous trophoblast of the placental bed.

• The development of PE during allogeneic pregnancy is accompanied by a decrease in the content of exosome components in syncytiotrophoblast cells

Thank you for attention!

1. Redman et al. 2012; 2. Shomer et al. 2013; 3 .Lee et al. 2012; 4. .Vargas et al. 2014 ; 5.Vargas et al. 2009; 6.Salomon et al. 2014

7.Lundholm et al. 2014

References